+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Modulation of human cytochrome P450 1A1-mediated oxidation of benzo[a]pyrene by NADPH:cytochrome P450 oxidoreductase and cytochrome b5



Modulation of human cytochrome P450 1A1-mediated oxidation of benzo[a]pyrene by NADPH:cytochrome P450 oxidoreductase and cytochrome b5



Neuro Endocrinology Letters 35(Suppl. 2): 105-113



Cytochrome P450 (CYP) 1A1 located in the membrane of endoplasmic reticulum is the most important enzyme in both activation and detoxification of carcinogenic benzo[a]pyrene (BaP), in combination with microsomal epoxide hydrolase (mEH). However, it is still not clearly explained how the electron transfer is mediated by NADPH:CYP oxidoreductase (POR), another component of the microsomal enzymatic system, on CYP1A1 during BaP oxidation, and whether microsomal cytochrome b5 might influence this electron transfer. High performance liquid chromatography (HPLC) was employed for separation of BaP metabolites formed by enzymatic systems containing human CYP1A1. Human CYP1A1 expressed with POR in eukaryotic and prokaryotic expression cellular systems, in microsomes of insect cells (Supersomes) and in a membrane fraction of Escherichia coli, respectively, and these enzyme systems reconstituted with purified cytochrome b5 were utilized to study BaP oxidation. Human CYP1A1 expressed in Supersomes oxidized BaP to seven metabolites [7,8- and 9,10-dihydrodiols, 1,6-dione, 3,6-dione, 3- and 9-phenols, and a metabolite with unknown structure (Mx)], whereas this enzyme expressed in membranes of E. coli formed only the metabolites 1,6- and 3,6-diones, 3- and 9-phenols, and Mx. Addition of cytochrome b5 to CYP1A1 expressed in the eukaryotic system led to a more than 2-fold increase in BaP metabolism, but had essentially no effect on BaP oxidation by CYP1A1 expressed in E. coli. The effect of cytochrome b5 on CYP1A1 conformation and the electron transfer to this enzyme may contribute to the cytochrome b5-mediated stimulation of BaP oxidation.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 058334131

Download citation: RISBibTeXText

PMID: 25638374


Related references

Cytochrome b5 and epoxide hydrolase contribute to benzo[a]pyrene-DNA adduct formation catalyzed by cytochrome P450 1A1 under low NADPH:P450 oxidoreductase conditions. Toxicology 318: 1-12, 2014

NADH:Cytochrome b5 Reductase and Cytochrome b5 Can Act as Sole Electron Donors to Human Cytochrome P450 1A1-Mediated Oxidation and DNA Adduct Formation by Benzo[a]pyrene. Chemical Research in Toxicology 29(8): 1325-1334, 2016

Cytochrome b 5 impacts on cytochrome P450-mediated metabolism of benzo[a]pyrene and its DNA adduct formation: studies in hepatic cytochrome b 5 /P450 reductase null (HBRN) mice. Archives of Toxicology 92(4): 1625-1638, 2018

Lack of electron transfer from cytochrome b5 in stimulation of catalytic activities of cytochrome P450 3A4. Characterization of a reconstituted cytochrome P450 3A4/NADPH-cytochrome P450 reductase system and studies with apo-cytochrome b5. Journal of Biological Chemistry 271(44): 27438-27444, 1996

Exposure to benzo(a) pyrene in the hepatic cytochrome P450 oxidoreductase (POR) null mouse: detoxification by hepatic cytochrome P450 is more important than metabolic activation. 2007

Role of acidic residues in the interaction of NADPH-cytochrome P450 oxidoreductase with cytochrome P450 and cytochrome c. Journal of Biological Chemistry 270(46): 27475-27480, 1995

Oxidation of carcinogenic benzo[a]pyrene by human and rat cytochrome P450 1A1 and its influencing by cytochrome b5 - a comparative study. Neuro Endocrinology Letters 34(Suppl. 2): 55-63, 2013

Stable expression of human cytochrome P450 3A4 in conjunction with human NADPH-cytochrome P450 oxidoreductase in V79 Chinese hamster cells. Archives of Biochemistry and Biophysics 332(2): 295-304, 1996

A fluorescence study of the interactions of benzo[a]pyrene, cytochrome P450c and NADPH-cytochrome P450 reductase. Biochemical Pharmacology 42(1): 97, 1991

Coexpression of human cytochrome P450 3A4 and human NADPH-cytochrome P450 oxidoreductase in V79 Chinese hamster cells. Naunyn-Schmiedeberg's Archives of Pharmacology 353(4 Suppl. ): R109, 1996

Optimization of yeast-expressed human liver cytochrome P450 3A4 catalytic activities by coexpressing NADPH-cytochrome P450 reductase and cytochrome b5. European Journal of Biochemistry 207(1): 109-116, 1992

Isolation of a new mouse cDNA clone: hybrid form of cytochrome P450 2b10 and NADPH-cytochrome P450 oxidoreductase. Biochemical and Biophysical Research Communications 226(3): 900-905, 1996

Structure and function of an NADPH-cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450. Journal of Biological Chemistry 284(17): 11374-11384, 2009

The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics 7(3): 203-210, 1997

Improvement in the expression efficiency of mammalian cytochrome P450 and NADPH-cytochrome P450 oxidoreductase in Saccharomyces cerevisiae. Biotechnology letters 19(5): 437-441, 1997